3-fluoro-4-(3-morpholin-4-ylpropoxy)benzaldehyde

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-fluoro-4-(3-morpholin-4-ylpropoxy)benzaldehyde
• 化学式: C₁₄H₁₈FNO₃
• 分子量: 267.3
• InChiKey: GAWLLATUOSHCHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-fluoro-4-oxo-N-piperidin-4-yl-4H-chromene-2-carboxamide 、 3-fluoro-4-(3-morpholin-4-ylpropoxy)benzaldehyde 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 N-(1-(3-fluoro-4-(3-morpholinopropoxy)benzyl)piperidin-4-yl)-7-fluoro-4-oxo-4H-chromene-2-carboxamide
  参考文献：
  名称：

  Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity

  摘要：

  A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor I (MCHrl) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkyl-amine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.068
• 作为产物：
  描述：

  4-(3-羟丙基)吗啉 、 3-氟-4-羟基苯甲醛 在 PS-Ph₃P 、 偶氮二甲酸二苄酯 作用下， 以 四氢呋喃 为溶剂， 生成 3-fluoro-4-(3-morpholin-4-ylpropoxy)benzaldehyde
  参考文献：
  名称：

  Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity

  摘要：

  A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor I (MCHrl) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkyl-amine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.068

文献信息

• SUBSTITUTED 1-AMINOPHTHALAZINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC APPLICATION THEREOF
  申请人：AUGEREAU Jean Michel

  公开号：US20090124624A1

  公开（公告）日：2009-05-14

  The invention concerns 1-amino-phthalazine derivatives of general formula (I): Wherein A, B, L, R, R 1 , R 2 , R 3 , R 4 , R 5 and R 7 are as defined herein. The invention also concerns the preparation of said compounds and their therapeutic use.

  这项发明涉及一般式(I)的1-氨基邻苯二酮衍生物：其中A、B、L、R、R1、R2、R3、R4、R5和R7如本文所定义。该发明还涉及所述化合物的制备及其治疗用途。
• DÉRIVÉS DE LA 1-AMINO-PHTALAZINE SUBSTITUEE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
  申请人：Sanofi-Aventis

  公开号：EP1940823A2

  公开（公告）日：2008-07-09
• [EN] SUBSTITUTED 1-AMINO-PHTHALZINE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] DÉRIVÉS DE LA 1-AMINO-PHTALAZINE SUBSTITUEE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
  申请人：SANOFI AVENTIS

  公开号：WO2007042660A2

  公开（公告）日：2007-04-19

  [EN] The invention concerns 1-amino-phthalazine derivatives of general formula (I), wherein: A, B = optionally substituted C_1-4 alkylene; L = single bond or C_1-2 alkylene, -CH=CH- or -C=C; the C_1-2 alkylene and -CH=CH- groups being optionally substituted, or L = cycloprop-1,2-diyl; R = H or C_1-5 alkyl, C_1-3 fluoroalkyl, C_3-6 cycloalkyl, -C(O)C_1-3 alkyl, C_1-3 alkylene-C_3-6 cylcoalkyl, -CH₂-C=CH, C_1-3 alkylene-NR_aR_b, C_1-3 alkylene-X-C_1-3 alkyl with X=O, SO₂; R₁ = aryl or a heteroaryl optionally substituted; R₂, R₃ = H, C_1-3 alkyl or C_1-3 fluoroalkyl, or R₂ and R₃ together form a cycloprop-1,1-diyl; R₄ = H or a C_1-5 alkyl, C_1-3 fluoroalkyl, C_3-6 cycloalkyl, C_1-3 alkylene-C_3-6 cycloalkyl, C_1-3 alkylene-C_3-6 cycloalkyl, C_1-3 alkylene-O-C_1-3 alkyl, or R₄ = C_1-3 alkylene-(OH), C_1-3 alkylene-X-C_1-3 alkyl where X = S, SO or SO₂, or R₄ = heterocycle, a C_1-3 alkylene-Nr_aR_b group, aryl, C_1-3 alkylene-aryl, -O-aryl, C_1-3 alkylene-O-aryl, C_1-3 alkylene-O-C_1-3 alkylene-aryl, heteroaryl or C_1-3 alkylene-heteroaryl, optionally substituted. R₅ = halogen or a C_1-5 alkyl, C_1-3 fluoroalkyl, C_1-5 alkoxy, C_1-3 fluoroalkoxy, C_1-3 alkylene-(OH), -CN, -X-C_1-3 alkyl where X = S, SO or SO₂, or R₅ = Nr_aR_b, C_{1 3} alkylene- Nr_aR_b, aryl, C_1-3 alkylene-aryl, -O-aryl or heteroaryl, optionally substituted; R₇ = H, halogen or a C_1-5 alkyl, C_1-3 fluoroalkyl, C_1-5 alkoxy, -COOH, -C(O)OC_1-5 alkyl, C_1-3 fluoroalkoxy, C_1-3 alkylene-(OH), -CN, -X-C_1-3 alkyl where X represents S, SO or SO₂, or R₇ = -Nr_aR_b, C_1-3 alkylene-Nr_aR_b,-C(O)-Nr_aR_b, -C(O)-C_1-3 alkyl, aryl, -O-aryl or heteroaryl, optionally substituted; in base or acid addition salt form, as well as in hydrate or solvate form. The invention also concerns the preparation of said compounds and their therapeutic use.
  [FR] L'invention concerne des dérivés de la 1-amino-phtalazine, de formule générale (I) A, B = C_1-4-alkylène éventuellement substitué ; L = liaison simple ou un C_1-2-alkylène, - CH=CH- ou -C=C- ; les groupes C_1-2-alkylène et -CH=CH- étant éventuellement substitués, ou bien L = cycloprop-1 ,2-diyle ; R = H ou C_1-5-alkyle, C_1-3-fluoroalkyle, C_3-6- cycloalkyle, -C(O)C_1-3-alkyle, C_1-3-alkylène-C_3-6-cycloalkyle, -CH₂-C=CH, C_1-3-alkylène- NR_aR_b, C_1-3-alkylène-X-C_1-3-alkyle avec X= O, SO₂ ; R₁ = aryle ou un hétéroaryle, éventuellement substitués ; R₂, R₃ = H, C_1-3-alkyle ou C_1-3-fluoroalkyle, ou bien R₂ et R₃ forment ensemble un cycloprop-1 , 1-diyle ; R₄ = H ou un C_1-5-alkyle, C_1-3-fluoroalkyle, C_3-6- cycloalkyle, C_1-3-alkylène-C_3-6-cycloalkyle, C_1-3-alkylène-O-C_1-3-alkyle, ou R₄= C_1-3- alkylène-(OH), C_1-3-alkylène-X-C_1-3-alkyle où X = S, SO ou SO₂, ou R₄ = hétérocycle, groupe C_1-3-alkylène-NR_aR_b, aryle, C_1-3-alkylène-aryle, -O-aryle, C_1-3-alkylène-O-aryle, C₁- 3-alkylène-O-C_1-3-alkylène-aryle, hétéroaryle ou C_1-3-alkylène-hétéroaryle, éventuellement substitués ; R₅ = H, halogène ou un C_1-5-alkyle, C_1-3-fluoroalkyle, C_1-5-alcoxy, C_1-3- fluoroalcoxy, C_1-3-alkylène-(OH), -CN, -X-C_1-3-alkyle où X = S, SO ou SO₂, ou R₅ = - NR_aR_b, C_1-3-alkylène-NR_aR_b, aryle, C_1-3-alkylène-aryle, -O-aryle ou hétéroaryle, éventuellement substitués ; R₇ = H, halogène ou un C_1-5-alkyle, C_1-3-fluoroalkyle, C_1-5- alcoxy, -COOH, -C(O)OC_1-5-alkyle, C_1-3-fluoroalcoxy, C_1-3-alkylène-(OH), -CN, -X-C_1-3- alkyle où X représente S, SO ou SO₂, ou R₇ = -NR_aR_b, C_1-3-alkylène-NR_aR_b, -C(O)- NR_aR_b, -C(O)-C_1-3-alkyle, aryle, -O-aryle ou hétéroaryle, éventuellement substitués ; à l'état de base ou de sel d'addition à un acide, ainsi qu'à l'état d'hydrate ou de solvat. Procédé de préparation et application en thérapeutique.
• Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity
  作者：Andrew S. Judd、Andrew J. Souers、Dariusz Wodka、Gang Zhao、Mathew M. Mulhern、Rajesh R. Iyengar、Ju Gao、John K. Lynch、Jennifer C. Freeman、H. Douglas Falls、Sevan Brodjian、Brian D. Dayton、Regina M. Reilly、Gary Gintant、James T. Limberis、Ann Mikhail、Sandra T. Leitza、Kathryn A. Houseman、Gilbert Diaz、Eugene N. Bush、Robin Shapiro、Victoria Knourek-Segel、Lisa E. Hernandez、Kennan C. Marsh、Hing L. Sham、Christine A. Collins、Philip R. Kym

  DOI：10.1016/j.bmcl.2006.11.068

  日期：2007.4

  A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor I (MCHrl) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkyl-amine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series. (c) 2006 Elsevier Ltd. All rights reserved.